UWCCC Tumor Microenvironment (TM) Program Summary Co-Leaders: Patricia Keely and David Beebe PROJECT SUMMARY/ABSTRACT Tumors are complex systems composed of tumor cells, stromal cells, soluble factors, and the extracellular matrix (ECM); together, these components constitute the tumor microenvironment. While cancer research has focused historically on studying and treating the tumor cell, it is now clear that the other components of the tumor microenvironment are active participants in tumor progression. For example, growth factors secreted by tumor cells attract immune cells into the tumor microenvironment; these immune cells in turn provide cytokines and other factors that stimulate stromal cell deposition and remodeling of ECM, which feedback to influence tumor cell behavior. Although the tumor microenvironment is undoubtedly important in the progression of several types of cancer, therapeutic approaches targeted against the microenvironment remain rare, in part, because knowledge in this area is insufficient. Therefore, it is the mission of the Tumor Microenvironment (TM) Program to identify microenvironmental changes that occur during tumorigenesis and analyze how the interactions between the tumor cell and microenvironmental components affect tumor formation, growth, progression, and ultimately metastasis. To accomplish these goals, the TM program fosters collaborations between its 32 members from 17 departments - basic scientists, clinicians, and bioengineers who specialize in the development of systems that mimic the in vivo environment and computational modeling of systems-level behaviors. TM program research is organized into three thematic areas: 1) Extracellular Matrix, 2) Engineering Approaches, and 3) Immune Interactions. Program members were supported by $3.0 million direct costs in NCI-funding and $10.6 million direct costs in total peer-reviewed cancer-related support, and were highly productive with 494 publications during the course of the last grant. Of these publications, 13% were intra- programmatic collaborations and 24% were inter-programmatic collaborations. In the year 2016 alone, nearly 50% of publications were collaborative with other institutions. Through these research efforts, members of the TM program are identifying new biomarkers and therapeutic approaches.